Project Summary Surgery remains the best therapeutic option for lung cancer, and approximately 7,400 Veterans and 63,500 non-Veterans undergo lung cancer surgery in the United States each year. However, 17-20% of patients develop local recurrences after lung cancer surgery. Once they recur, their 2 year survival is less than 15%. Patients typically develop local recurrences in two places: positive surgical margins and regional metastases. Our goal is to improve the intraoperative identification of tumor cells at positive margins and regiona metastases that may be missed by a surgeon during a pulmonary resection. Improved identification of tumor cells will result in superior disease clearance and more accurate clinical staging. We hypothesize that targeted fluorescent imaging during surgery will improve identification of positive margins and metastases. Since folate receptor alpha (FRa) is expressed on 55% of resectable lung cancer, we will utilize a fluorescent probe (folate- FITC) that targets these tumors. In order to test our hypothesis, we will investigate the following objectives: 1) Evaluate the safety, feasibility and applicability of performing intraoperative imaging during a pulmonary resection. 2) To assess the intraoperative benefits of image-guided surgery using a folate receptor-targeted fluorescent probe. 3) To conduct ex vivo correlative studies on the lung tumors following intraoperative imaging. This technology has the potential to fundamentally transform cancer surgery in the United States. As real-time imaging provides more information to the surgeon, more personalized and directed operations can be conducted. This work will allow for more preservation of normal tissue, decreased morbidity, decreased surgical time, increased surgical confidence, improved cancer detection, decreased unnecessary surgery and ultimately improved tumor free survival. This technology should transform clinical surgery from an art that depends fully on the human factor to a procedure that has precision and fail safes.